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Abstract

This thesis discusses three distinct medicinal inorganic chemistry projects involving the design of well-tailored ligands for diagnostic and therapeutic applications. In one study, combination agents for diabetes therapy were developed utilizing vanadium and the thiazolidinediones. A hybrid approach was used whereby the two aforementioned active agents were combined into one molecule. A series of bifunctional thiazolidinedione-containing pro-ligands were synthesized and complexed to vanadium. One vanadium complex, and associated ligand precursor, were found to be quite effective in lowering plasma glucose levels in an acute animal model of diabetes. In another study numerous tetrahydrosalen compounds were synthesized and evaluated for potential use in Alzheimer's disease chelation therapy. Glycosylated pro-drug forms were developed to minimize systemic metal chelation and potentially enhance brain uptake. Solution studies of two tetrahydrosalen ligands exhibiting remote glycosylation indicated that these compounds form neutral complexes with Cu2 + and Zn2 + at physiological pH (7.4). The final study investigated the chemistry of carbohydrate-appended metal (Re and 9 9 mTc) complexes for use as target-specific radiopharmaceuticals. A series of bidentate and tridentate carbohydrate-containing ligands were attached to the/ac-{M(CO)3}+(M = Re or 9 9 mTc) core and in all cases the carbohydrate moiety was determined to remain pendant. The bidentate analogs were found to be more susceptible towards ligand exchange than were the tridentate compounds. Clearly matching the tridentate binding capability of carbohydrate-appended ligands to the fac-{M(CO)3}+ core greatly stabilized the resulting complexes to ligand substitution processes in vitro.